Prior art endoscopes have conventionally been used in diagnosis and treatment where a fluorescent substance having an affinity to a lesion, such as cancer, has been previously administered into a subject's body and excitation light that excites the fluorescent substance is then irradiated onto tissue of the subject so that fluorescent emissions from the fluorescent substance that deposits at the lesion can be detected.
For example, Japanese Laid-Open Patent Application H10-201707 describes a prior art endoscope wherein indocyanine green derivative labeled antibodies have been previously introduced into the living tissue. The lesions then emit fluorescent light when excited by infrared light, with the infrared light being readily transmitted by living tissue without damaging the living tissue. This enables the lesions to be observed by detecting the fluorescent light emissions while the light caused by self-fluorescence (autofluorescence) of the living tissues is blocked in order to aid in preventing lesions that are deep inside the living tissue from being overlooked.
Indocyanine green derivative labeled antibodies attach to human IgG as a fluorescent agent and are excited by excitation light having a peak wavelength of approximately 770 nm. Such labeled antibodies produce fluorescence having a peak wavelength of approximately 810 nm. Japanese Laid-Open Patent Application H10-201707 illuminates living tissue of interest that has previously been administered such a fluorescent agent with light from a light source having wavelengths in the range of approximately 770-780 nm, and then detects light wavelengths that are emitted from the living tissue in the wavelength range of approximately 810-820 nm so as to determine the presence of a lesion.
It is a well known fact that the earlier cancer is detected in a patient the less invasive the treatment; moreover, the treatment is generally more effective so as to provide improved survivability. Early detection of cancer in patients is a goal embraced by workers in the life science/medical field as well as by the population as a whole. However, cancer cells in the earliest stage show only meager morphologic changes from normal cells, and thus, conventional techniques that focus primary on morphologic changes in cells for determining the presence of cancer are not applicable for detecting cancer in the earliest stage.
Furthermore, cancer in the earliest stage typically develops several millimeters deep within the surface of living tissue. In addition, living tissue scatters light in a sufficiently intense manner that the living tissue layer above the cancerous region blocks observation of the cancer. This becomes a remarkably adverse factor in solving the problem of detecting cancer in the earliest stage. Of course, the fact that the tissues to be observed are within a living body is also an adverse factor.
Attempts have been made to develop a technique that combines using infrared light, which can reach deep inside living tissue with the infrared light being minimally scattered or absorbed, with a technology that introduces a plurality of different fluorescent labels into a plurality of different specific proteins. The proteins appear as cancer develops within living cells, and such a technique would enable the detection of cancer in its earliest stage and should enable a diagnosis to be made of whether the cancer has become malignant. In addition to endoscopes, diagnosis systems for cancer include CT, MRI, and PET scanning devices. Each of these devices uses a sensor that is externally provided in order to depict in three dimensions the interior regions of a human body and each is a non-invasive organ examination tool. Such devices can detect cancer once the cancerous region has grown to a size of approximately 1 cm or larger. However, the resolution of these devices is not yet sufficient to enable cancer to be detected in its earliest stage or to enable a diagnosis to be made of whether the cancer has become malignant.
Research in life science such as genomics and proteomics has determined that cancer develops as a pre-cancerous lesion and the lesion gradually grows and transforms into metastatic, infiltrative cancer cells. Cancer is a genetic disease, and it is believed that a succession of genetic mutations causes the cells to become malignant. Gene defects are triggered by the expression (i.e., the presence) of specific proteins in the cell. A diagnosis of malignancy concerning a tumor or cancer can be made only when specific proteins for plural types of cancers are present, or when genes that cause defects are detected.
According to recent reports, tumors can be diagnosed as being either benign or malignant when several types of proteins that are specifically expressed in cancer cells are detected. The diagnosis of the malignancy of a tumor is assured with improved accuracy if various additional types of proteins are detected. Theoretically, plural cancer-specific proteins in a living body can be labeled with different fluorescent light producing substances. Then, the different fluorescent light producing substances can be detected so as to determine the presence of cancer-specific proteins in order to verify a malignancy.
Living tissue scatters light in a sufficiently intense manner that illuminated living tissue is difficult to see through. However, living tissue rarely scatters or absorbs significant amounts of light in the near-infrared to infrared range. For this reason, near-infrared and infrared wavelengths of light are often used in lesion diagnosis techniques. Light of this wavelength range is used as the excitation light for the fluorescent labels so that fluorescent labels that are distributed deep inside a living tissue will emit fluorescence, thereby aiding in the detection of cancer at an early stage.
In the present invention, plural cancer-specific proteins are labeled with different fluorescent light producing substances that fluoresce in the near-infrared to infrared range, and these wavelengths are then detected using an endoscope so as to reveal the presence of cancer-specific proteins in cells that may be several millimeters deep within a living body. It is desirable that the respective fluorescent labels have narrow fluorescent wavelength emissions so that plural fluorescent labels can be introduced and detected, thus increasing the number of types of cancer-specific proteins that can be detected and thereby improving the accuracy of such an endoscopic diagnosis.
Fluorescent labels that bind to cancer-specific proteins are introduced into living tissues, and plural fluorescent wavelengths are detected so that cancer-specific proteins that correspond to the fluorescent wavelengths can be detected. Thus, plural fluorescent labels can be used for fluorescence detection so that cancer in a patient can be diagnosed as being either benign or malignant at an earlier stage.
In prior art endoscopes, the wavelength used can be varied only by varying the wavelength of the light source, and thus a technique for separating plural wavelengths in the near-infrared range is not available in the detection component. Therefore, in prior art endoscopes, plural fluorescent wavelengths that emit fluorescence in the near-infrared range when excited by illumination cannot be detected even when such labels have been previously introduced into living tissue that is to be observed.